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Hear This: Dolby Family Puts More Cash Into Alzheimer Alternatives

[Updated, 7/27/15, 7:35pm. See below.] After a battle with Alzheimer’s disease, audio engineering pioneer Ray Dolby died in 2013. Now his family is using the fortune he left behind to help find treatments that take a different tack than much of the work in the field to date.

After making its public debut last year, Dolby Family Ventures is now working on an unusual plan to fund high-risk Alzheimer’s treatments that are still in the early research stages at San Francisco’s Gladstone Institutes, a private nonprofit that shares faculty with the University of California, San Francisco.

Traditionally a basic research center, Gladstone has been branching out under R. Sanders “Sandy” Williams, the former dean of Duke University’s School of Medicine who has also served as a director at big drug companies. Williams became Gladstone president in 2010.

For the Dolby collaboration, Gladstone has created a for-profit entity, Cure Network Ventures, which will serve as a holding company for individually funded R&D programs, according to Stephen Freedman, Gladstone’s vice president of corporate liaison and ventures. Freedman will also serve as Cure Network Ventures CEO; a majority of the startup’s board members will come from outside Gladstone.

Ray Dolby’s son, David, who runs the family venture group, could not be reached for comment, but in an interview last fall, he told Xconomy that the fund would be willing to make bets that run contrary to conventional wisdom in the Alzheimer’s field. “We’re not in the flavor-of-the-month investing business here,” he said.

He described a $500,000 seed investment in the startup Cortexyme, which is investigating the ties between bacterial infection and Alzheimer’s, as “a perfect example of what we’re willing to do.” (Last fall, the fund also put $2 million into PharmatrophiX; it has also invested in Cogstate, which is developing better cognitive tests for clinical trials.)

Two Gladstone programs are being funded for now with an undisclosed amount of Dolby cash. One focuses on tau, one of two proteins that form abnormal clumps in the brains of Alzheimer’s patients. The other examines the role in Alzheimer’s of ion channels, which are pores in the membranes of cells that allow signals to pass through. Both come from the lab of Lennart Mucke, director of the Gladstone Institute of Neurological Disease. (Gladstone’s other two core areas are cardiology and immunology/virology.)

[Updated with comments from Lennart Mucke.] There are several different forms of tau, including one that seems to travel from neuron to neuron. Mucke said that the tau program being funded will focus on overall reduction of the protein in the brain, not on any one form. “It’s not clear what the most disease-causing form of tau is,” he said. “There is a lot of debate. In the meantime, overall reduction is an attractive strategy.” He declined to say if his team will use a small molecule, an antibody, or some other form of intervention.

The second program will try to lower the amount of stimulation neurons receive through their ion channels. Too much excitation can be toxic, said Mucke, and he’d like to find a way to shift the signal-to-noise ratio.

If all goes well, said Freedman, the two programs could reach human clinical trials in four or five years. Before that happens, the partners need to identify a lead drug candidate from each program to move forward, a process that could take a couple years.

Dolby and Gladstone will turn to German biotech Evotec for industrial expertise. Evotec is a contract research firm, but it will be an active participant in R&D decisions and could end up as an equity investor in each program. “We don’t have their drug discovery and fine-tuning and improvement capabilities in house,” said Mucke. “We can marry those with our biological insights.”

Once the drugs are in clinical trials, the partners will need much larger sources of cash, into the tens of millions of dollars.

When deciding which programs to move into Cure Network Ventures, people from all three groups—Gladstone, Dolby, and Evotec—voted on the two best from eight or nine research projects from Gladstone’s labs, said Freedman.

The Dolby investment in Alzheimer’s comes at a time when a main thrust of R&D to treat the disease is enjoying somewhat of a revival. For years, developers thought clearing clumps of the misfolded protein amyloid beta from the brains of patients would alter the course of the disease. In trial after trial, however, that clearance had no effect.

Those failures have prompted companies to test amyloid clearance in patients whose disease is far less advanced. In one high-profile attempt, Biogen (NASDAQ: BIIB) is confident enough in Phase 1 results that it is moving its drug aducanumab into large Phase 3 trials. Mucke, a proponent of using multiple strategies to attack Alzheimer’s, which he calls a disease with “multifactorial pathomechanisms,” said those hopeful results show that “we haven’t maxed out the anti-amyloid beta treatments” yet.

Treatments that address tau—another protein that goes haywire in the brains of Alzheimer’s patients—have not received nearly the same level of attention or funding. At Gladstone, Mucke’s work has gone beyond amyloid-beta to investigate tau and other proteins and cells that might play a role in Alzheimer’s mysterious and complicated pathology, as he and a co-author wrote in this 2012 paper.